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Childhood morbidity and mortality of diarrhoeal diseases are high, particularly in low-income countries and noroviruses and sapoviruses are among the most frequent causes worldwide. Their epidemiology and diversity remain not well studied in many African countries. To assess the positivity rate and the diversity of sapoviruses and noroviruses in Northwest Ethiopia, during November 2015 and April 2016, a total of 450 faecal samples were collected from outpatient children aged <5 years who presented with diarrhoea. Samples were screened for noroviruses and sapoviruses by real-time RT-PCR. Partial VP1 genes were sequenced, genotyped and phylogenetically analysed. Norovirus and sapovirus stool positivity rate was 13.3% and 10.0%, respectively. Noroviruses included GII.4 (35%), GII.6 (20%), GII.17 (13.3%), GII.10 (10%), GII.2 (6.7%), GII.16 (5%), GII.7 (3.3%), GII.9, GII.13, GII.20 and GI.3 (1.7% each) strains. For sapoviruses, GI.1, GII.1 (20.0% each), GII.6 (13.3%), GI.2 (8.9%), GII.2 (11.1%), GV.1 (8.9%), GIV.1 (6.7%), GI.3 and GII.4 (2.2% each) genotypes were detected. This study demonstrates a high genetic diversity of noroviruses and sapoviruses in Northwest Ethiopia. The positivity rate in stool samples from young children with diarrhoea was high for both caliciviruses. Continued monitoring is recommended to identify trends in genetic diversity and seasonal variations.
Gastropods often show signs of unsuccessful attacks by durophagous predators in the form of healed scars in their shells. As such, fossil gastropods can be taken as providing a record of predation through geological time. However, interpreting the number of such scars has proved to be problematic—Would a low number of scars mean a low rate of attack or a high rate of success, for example? Here we develop a model of population dynamics among individuals exposed to predation, including both lethal and nonlethal attacks. Using this model, we calculate the equilibrium distributions of ages and healed scars in the population and among fossilized specimens, based on the assumption that predation is independent of age or scar number. Based on these results, we formally show that the rates of attack and success cannot be disambiguated without further information about population structure. Nevertheless, by making the assumptions that the non-durophagous predatory death rate is both constant and low, we show that it is possible to use relatively small assemblages of gastropods to produce accurate estimates of both attack and success rates, if the overall death rate can be estimated. We consider likely violations of the assumptions in our model and what sort of information would be required to solve this problem in these more general cases. However, it is not easy to extract the relevant information from the fossil record: a variety of important biases are likely to intervene to obscure the data that gastropod assemblages may yield. Nonetheless, the model provides a theoretical framework for interpreting summary data, including for comparison between different assemblages.
The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)].
Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes.
Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome.
This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the ‘limbic’ AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.
The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6–4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.
The transfer of pathogens may spread antimicrobial resistance and lead to healthcare-acquired infections. We performed a systematic literature review to generate estimates of pathogen transfer in relation to healthcare provider (HCP) activities.
For this systematic review and meta-analysis, Medline/Ovid, EMBASE, and the Cochrane Library were searched for studies published before July 7, 2017. We reviewed the literature, examining transfer of pathogens associated with HCP activities. We included studies that (1) quantified transfer of pathogens from a defined origin to a defined destination surface; (2) reported a microbiological sampling technique; and (3) described the associated activity leading to transfer. For studies reporting transfer frequencies, we extracted data and calculated the estimated proportion using Freeman-Tukey double arcsine transformation and the DerSimonian-Laird random-effects model.
Of 13,121 identified articles, 32 were included. Most articles (n=27, 84%) examined transfer from patients and their environment to HCP hands, gloves, and gowns, with an estimated proportion for transfer frequency of 33% (95% confidence interval [CI], 12%–57%), 30% (95% CI, 23%–38%) and 10% (95% CI, 6%–14%), respectively. Other articles addressed transfer involving the hospital environment and medical devices. Risk factor analyses in 12 studies suggested higher transfer frequencies after contact with moist body sites (n=7), longer duration of care (n=5), and care of patients with an invasive device (n=3).
Recognizing the heterogeneity in study designs, the available evidence suggests that pathogen transfer to HCPs occurs frequently. More systematic research is urgently warranted to support targeted and economic prevention policies and interventions.
In this paper, we propose a novel type of serial robot with minimal actuation. The robot is a serial rigid structure consisting of multiple links connected by passive joints and of movable actuators. The novelty of this robot is that the actuators travel over the links to a given joint and adjust the relative angle between the two adjacent links. The joints passively preserve their angles until one of the actuators moves them again. This actuation can be applied to any serial robot with two or more links. This unique configuration enables the robot to undergo the same wide range of motions typically associated with hyper-redundant robots but with much fewer actuators. The robot is modular and its size and geometry can be easily changed. We describe the robot's mechanical design and kinematics in detail and demonstrate its capabilities for obstacle avoidance with some simulated examples. In addition, we show how an experimental robot fitted with a single mobile actuator can maneuver through a confined space to reach its target.
To examine the feasibility of implementing nine behavioural economics-informed strategies, or ‘nudges’, that aimed to encourage home dinner vegetable intake among low-income children.
Caregivers were assigned six of nine strategies and implemented one new strategy per week (i.e. 6 weeks) during three dinner meals. Caregivers recorded child dinner vegetable intake on the nights of strategy implementation and rated the level of difficulty for assigned strategies. Baseline data on home vegetable availability and child vegetable liking were collected to assess overall strategy feasibility.
Participants’ homes in a large Midwestern metropolitan area, USA.
Pairwise comparisons showed that child dinner vegetable intake for the strategy ‘Serve at least two vegetables with dinner meals’ was greater than intake for each of two other strategies: ‘Pair vegetables with other foods the child likes’ and ‘Eat dinner together with an adult(s) modelling vegetable consumption’. Overall, caregivers’ mean rating of difficulty for implementing strategies was 2·6 (1=‘not difficult’, 10=‘very difficult’). Households had a mean of ten different types of vegetables available. Children reported a rating ≥5 for seventeen types of vegetable on a labelled hedonic scale (1=‘hate it’, 5–6=‘it’s okay’, 10=‘like it a lot’).
Behavioural economics-informed strategies are feasible to implement during dinner meals, with some strategies differing by how much they influence vegetable intake among low-income children in the home.
Cortisol is the primary output of the hypothalamic–pituitary–adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function.
In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80–19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type.
Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone.
Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.
This study details the characterization of a glass sample exposed to hyperalkaline water and calcium-rich sediment for an extended time period (estimated as 2 - 70 years) at a lime (CaO) waste site in the UK. We introduce this site, known as Peak Dale, in reference to its use as a natural analogue for nuclear waste glass dissolution in the high pH environment of a cementitious engineered barrier of a geological disposal facility. In particular, a preliminary assessment of alteration layer chemistry and morphology is described and the initiation of a long-term durability assessment is outlined.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.
We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.
Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.
During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.
After a little more than forty years of work related to the interplanetary plasma and the heliosphere the IAU's Commission 49 was formally discontinued in 2015. The commission started its work when the first spacecraft were launched to measure the solar wind in–situ away from Earth orbit, both inward and outward from 1 AU. It now hands over its activities to a new commission during an era of space research when Voyager 1 measures in–situ the parameters of the local interstellar medium at the edge of the heliosphere. The commission will be succeeded by C.E3 with a similar area of responsibility but with more focused specific tasks that the community intends to address during the coming several years. This report includes a short description of the motivation for this commission and of the historical context. It then describes work from 2012 to 2015 during the present solar cycle 24 that has been the weakest in the space era so far. It gave rise to a large number of studies on solar energetic particles and cosmic rays. Other studies addressed e.g. the variation of the solar wind structure and energetic particle fluxes on long time scales, the detection of dust in the solar wind and the Voyager measurements at the edge of the heliosphere. The research is based on measurements from spacecraft that are at present operational and motivated by the upcoming Solar Probe + and Solar Orbiter missions to explore the vicinity of the Sun. We also report here the progress on new and planned radio instruments and their importance for heliospheric studies. Contributors to this report are Carine Briand, Yoichiro Hanaoka, Eduard Kontar, David Lario, Ingrid Mann, John D. Richardson.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
There is increasing evidence that Mars may have once been a habitable environment. Gypsum is targeted in the search for Martian biosignatures because it can host extensive cryptoendolithic communities in extreme terrestrial environments and is widespread on Mars. In this study the viability of using different spectroscopy-based techniques to identify the presence of gypsum endolithic communities was investigated by analysing various cryptoendoliths collected from the Lake St. Martin impact crater (LSM), a Mars analogue site found in Manitoba, Canada. Concurrently, the cryptoendolithic microbial community structure present was also analysed to aid in assigning spectroscopic features to microbial community members. Two main morphologies of endolithic communities were collected from gypsum deposits at LSM: true cryptoendolithic communities and annular deposits on partially buried boulders and cobbles <1 cm below the soil surface. Endolithic communities were found to be visibly present only in gypsum with a high degree of translucency and could occur as deep as 3 cm below the exterior surface. The bacterial community was dominated by a phylum (Chloroflexi) that has not been previously observed in gypsum endoliths. The exterior surfaces of gypsum boulders and cobbles are devoid of spectroscopic features attributable to organic molecules and detectable by reflectance, Raman, or ultraviolet-induced fluorescence spectroscopies. However, exposed interior surfaces show unique endolithic signatures detectable by each spectroscopic technique. This indicates that cryptoendolithic communities can be detected via spectroscopy-based techniques, provided they are either partially or fully exposed and enough photon–target interactions occur to enable detection.
The ability to discriminate biogenic from abiogenic calcium carbonate (CaCO3) would be useful in the search for extant or extinct life, since CaCO3 can be produced by both biotic and abiotic processes on Earth. Bioprecipitated CaCO3 material was produced during the growth of heterotrophic microbial isolates on medium enriched with calcium acetate or calcium citrate. These biologically produced CaCO3, along with natural and synthetic non-biologically produced CaCO3 samples, were analysed by reflectance spectroscopy (0.35–2.5 μm), Raman spectroscopy (532 and 785 nm), and laser-induced fluorescence spectroscopy (365 and 405 nm excitation). Optimal instruments for the discrimination of biogenic from abiogenic CaCO3 were determined to be reflectance spectroscopy, and laser-induced fluorescence spectroscopy. Multiple absorption features in the visible light region occurred in reflectance spectra for most biogenic CaCO3 samples, which are likely due to organic pigments. Multiple fluorescence peaks occurred in emission spectra (405 nm excitation) of biogenic CaCO3 samples, which also are best attributed to the presence of organic compounds; however, further analyses must be performed in order to better determine the cause of these features to establish criteria for confirming the origin of a given CaCO3 sample. Raman spectroscopy was not useful for discrimination since any potential Raman peaks in spectra of biogenic carbonates collected by both the 532 and 785 nm lasers were overwhelmed by fluorescence. However, this also suggests that biogenic carbonates may be identified by the presence of this organic-associated fluorescence. No reliable spectroscopic differences in terms of parameters such as positions or widths of carbonate-associated absorption bands were found between the biogenic and abiogenic carbonate samples. These results indicate that the presence or absence of organic matter intimately associated with carbonate minerals is the only potentially useful spectral discriminator for the techniques that were examined, and that multiple spectroscopic techniques are capable of detecting the presence of associated organic materials. However, the presence or absence of intimately associated organic matter is not, in itself, an indicator of biogenicity.